U.S. patent application number 09/929033 was filed with the patent office on 2002-01-31 for stable isotope measurement method and apparatus by spectroscopy.
This patent application is currently assigned to Otsuka Pharmaceutical Co., Ltd.. Invention is credited to Kubo, Yasuhiro, Mori, Masaaki, Tsutsui, Kazunori.
Application Number | 20020011569 09/929033 |
Document ID | / |
Family ID | 26338693 |
Filed Date | 2002-01-31 |
United States Patent
Application |
20020011569 |
Kind Code |
A1 |
Mori, Masaaki ; et
al. |
January 31, 2002 |
Stable isotope measurement method and apparatus by spectroscopy
Abstract
In accordance with the present invention, a test gas sample
containing carbon dioxide .sup.13CO.sub.2 as a component gas is
introduced into a cell, then the absorbance of light transmitted
therethrough at a wavelength suitable for the component gas
.sup.13CO.sub.2 is determined, and the concentration of the
component gas is determined on the basis of a calibration curve
prepared through measurement on test gas samples each containing
the component gas in a known concentration. Further, the
concentration of water vapor contained in the test gas sample is
measured, and the concentration of the component gas in the test
gas sample is corrected in accordance with the measured water vapor
concentration on the basis of a correction curve prepared through
measurement on the test gas samples each containing water vapor in
a known concentration. With the spectrometry, the concentration
ratio of the component gas can precisely be determined and
corrected by measuring the moisture content in the test gas
sample.
Inventors: |
Mori, Masaaki; (Osaka,
JP) ; Kubo, Yasuhiro; (Shiga, JP) ; Tsutsui,
Kazunori; (Osaka, JP) |
Correspondence
Address: |
FINNEGAN, HENDERSON, FARABOW, GARRETT &
DUNNER LLP
1300 I STREET, NW
WASHINGTON
DC
20005
US
|
Assignee: |
Otsuka Pharmaceutical Co.,
Ltd.
|
Family ID: |
26338693 |
Appl. No.: |
09/929033 |
Filed: |
August 15, 2001 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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09929033 |
Aug 15, 2001 |
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09341045 |
Jul 1, 1999 |
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09341045 |
Jul 1, 1999 |
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PCT/JP98/00097 |
Jan 12, 1998 |
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Current U.S.
Class: |
250/339.13 |
Current CPC
Class: |
G01N 21/3504 20130101;
G01N 33/0006 20130101 |
Class at
Publication: |
250/339.13 |
International
Class: |
G01N 021/35 |
Foreign Application Data
Date |
Code |
Application Number |
Jan 14, 1997 |
JP |
9-004844 |
Jan 14, 1997 |
JP |
9-004845 |
Claims
1. A stable isotope measurement method for spectrometrically
analyzing an isotopic gas by introducing a test gas sample
containing a component gas into a cell, measuring an intensity of
light transmitted therethrough at a wavelength suitable for the
component gas, and processing data of the light intensity to
determine a concentration of the component gas, the component gas
being carbon dioxide .sup.13CO.sub.2, the method comprising: a
first step of introducing the test gas sample into the cell and
determining an absorbance of light transmitted therethrough at the
wavelength suitable for the component gas; a second step of
determining a concentration of the component gas in the test gas
sample on the basis of a calibration curve prepared through
measurement on gas samples each containing the component gas in a
known concentration; and a third step of measuring a concentration
of water vapor contained in the test gas sample and correcting the
concentration of the component gas in the test gas sample in
accordance with the measured water vapor concentration on the basis
of a correction curve prepared through measurement on gas samples
each containing water vapor in a known concentration.
2. A stable isotope measurement method for spectrometrically
analyzing an isotopic gas by introducing a test gas sample
containing a plurality of component gases into a cell, measuring
intensities of light transmitted therethrough at wavelengths
suitable for the respective component gases, and processing data of
the light intensities to determine a concentration ratio between
the component gases, the component gases being carbon dioxide
.sup.12CO.sub.2 and carbon dioxide .sup.13CO.sub.2, the method
comprising: a first step of introducing the test gas sample into
the cell and determining absorbances of light transmitted
therethrough at the wavelengths suitable for the respective
component gases; a second step of determining a concentration ratio
between the component gases in the test gas sample on the basis of
a calibration curve prepared through measurement on gas samples
each containing the component gases in known concentrations; and a
third step of measuring a concentration of water vapor contained in
the test gas sample and correcting the concentration ratio between
the component gases in the test gas sample in accordance with the
measured water vapor concentration on the basis of a correction
curve prepared through measurement on gas samples each containing
water vapor in a known concentration.
3. A stable isotope measurement method for spectrometrically
analyzing an isotopic gas as set forth in claim 2, wherein the
correction curve in the third step is prepared by determining
absorbances at the wavelengths suitable for the respective
component gases for the plurality of gas samples containing water
vapor in different concentrations, then determining concentrations
of or concentration ratios between the respective component gases
in the gas samples on the basis of the calibration curve, and
plotting ratios or differences between the concentrations of or the
concentration ratios between the respective component gases in the
gas samples thus determined with respect to the water vapor
concentrations of the gas samples, and the correction in the third
step is achieved by obtaining a concentration correction value or a
concentration ratio correction value for the component gases by
fitting the water vapor concentration of the test gas sample
obtained in the third step to the correction curve, and then
dividing the concentrations of or the concentration ratio between
the respective component gases in the test gas sample obtained in
the second step by the concentration correction value or the
concentration ratio correction value obtained on the basis of the
correction curve, or subtracting the concentration correction value
or the concentration ratio correction value from the concentrations
of or the concentration ratio between the respective component
gases in the test gas sample.
4. A stable isotope measurement apparatus for spectrometrically
analyzing an isotopic gas by introducing a test gas sample
containing a plurality of component gases into a cell, measuring
intensities of light transmitted therethrough at wavelengths
suitable for the respective component gases, and processing data of
the measured light intensities by data processing means to
determine a concentration ratio between the component gases,
wherein the component gases are carbon dioxide .sup.12CO.sub.2 and
carbon dioxide .sup.13CO.sub.2, the data processing means
comprises: absorbance calculation means for determining absorbances
of light transmitted through the test gas sample introduced into
the cell on the basis of the light intensities measured at the
wavelengths suitable for the respective component gases;
concentration calculation means for calculating a concentration
ratio between the component gases in the test gas sample on the
basis of a calibration curve prepared through measurement on gas
samples each containing the component gases in known
concentrations; water vapor concentration measuring means for
measuring a concentration of water vapor contained in the test gas
sample; and correction means for correcting the concentration ratio
between the component gases in the test gas sample in accordance
with the measured water vapor concentration on the basis of a
correction curve prepared through measurement on gas samples each
containing water vapor in a known concentration.
5. A stable isotope measurement method for spectrometrically
analyzing an isotopic gas, which comprises the steps of introducing
a test gas sample containing carbon dioxide .sup.12CO.sub.2 and
carbon dioxide .sup.13CO.sub.2 as component gases into a cell,
determining absorbances of light transmitted therethrough at
wavelengths suitable for the respective component gases,
determining concentrations of the respective component gases in the
test gas sample on the basis of calibration curves prepared through
measurement on gas samples each containing the component gases in
known concentrations, wherein two test gas samples are sampled from
a single subject and, if a CO.sub.2 concentration of one of the
test gas samples is higher than a CO.sub.2 concentration of the
other test gas sample, the one test gas sample is diluted with air
to a CO.sub.2 concentration level equivalent to that of the other
test gas sample for measurement of the concentration ratios
.sup.13CO.sub.2/.sup.12CO.sub.2 in the respective test gas
samples.
6. A stable isotope measurement method for spectrometrically
analyzing an isotopic gas as set forth in claim 5, which comprises
the steps of introducing a test gas sample containing carbon
dioxide .sup.12CO.sub.2 and carbon dioxide .sup.13CO.sub.2 as
component gases into a cell, determining absorbances of light
transmitted therethrough at wavelengths suitable for the respective
component gases, determining concentrations of the respective
component gases in the test gas sample on the basis of calibration
curves prepared through measurement on gas samples each containing
the component gases in known concentrations, wherein (a) first and
second test gas samples are sampled from a single subject and
CO.sub.2 concentrations of the first and second test gas samples
are measured in a preliminary measurement, and (b) if the measured
CO.sub.2 concentration of the first test gas sample is higher than
the measured CO.sub.2 concentration of the second test gas sample,
a concentration ratio .sup.13CO.sub.2/.sup.12CO.sub.2 in the first
test gas sample is measured after the first test gas sample is
diluted with air to a CO.sub.2 concentration level equivalent to
that of the second test gas sample in a main measurement, and (c) a
concentration ratio .sup.13CO.sub.2/.sup.12CO.sub.2 in the second
test gas sample is measured in the main measurement.
7. A stable isotope measurement method for spectrometrically
analyzing an isotopic gas as set forth in claim 5, which comprises
the steps of introducing a test gas sample containing carbon
dioxide .sup.12CO.sub.2 and carbon dioxide .sup.13CO.sub.2 as
component gases into a cell, determining absorbances of light
transmitted therethrough at wavelengths suitable for the respective
component gases, determining concentrations of the respective
component gases in the test gas sample on the basis of calibration
curves prepared through measurement on gas samples each containing
the component gases in known concentrations, wherein (a) first and
second test gas samples are sampled from a single subject and
CO.sub.2 concentrations of the first and second test gas samples
are measured in a preliminary measurement, (b) if the measured
CO.sub.2 concentration of the first test gas sample is lower than
the measured CO.sub.2 concentration of the second test gas sample,
a concentration ratio .sup.13CO.sub.2/.sup.12CO.sub.2 in the first
test gas sample is measured as it is in a main measurement, and (c)
a concentration ratio .sup.13CO.sub.2/.sup.12CO.sub.2 in the second
test gas sample is measured after the second test gas sample is
diluted with air to a CO.sub.2 concentration level equivalent to
that of the first test gas sample in the main measurement.
Description
DESCRIPTION
[0001] 1. Technical Field of the Invention
[0002] Isotopic analyses are useful for diagnosis of a disease in a
medical application, in which metabolic functions of a living body
can be determined by measuring a change in the concentration or
concentration ratio of an isotope after administration of a drug
containing the isotope. In the other fields, the isotopic analyses
are used for studies on the photosynthesis and metabolism of
plants, and for ecological tracing in a geochemical
application.
[0003] The present invention relates to stable isotope measurement
methods and apparatus for spectrometrically measuring the
concentration or concentration ratio of an isotopic gas on the
basis of the light absorption characteristics of the isotope.
[0004] 2. Background Art It is generally known that gastric ulcer
and gastritis are caused by bacteria called helicobacter pylori
(HP) as well as by a stress.
[0005] If the HP is present in the stomach of a patient, an
antibiotic or the like should be administered to the patient for
bacteria removal treatment. Therefore, it is indispensable to check
if the patient has the HP. The HP has a strong urease activity for
decomposing urea into carbon dioxide and ammonia.
[0006] Carbon has isotopes having mass numbers of 12, 13 and 14,
among which .sup.13C having a mass number of 13 is easy to handle
because of its non-radioactivity and stability.
[0007] If the concentration of .sup.13CO.sub.2 as a final metabolic
product or the concentration ratio of .sup.13CO.sub.2 to
.sup.12CO.sub.2 in breath of a patient is successfully measured
after urea labeled with the isotope .sup.13C is administered to the
patient, the presence of the HP can be confirmed.
[0008] However, the concentration ratio of .sup.13CO.sub.2 to
.sup.12CO.sub.2 in naturally occurring carbon dioxide is 1:100.
Therefore, it is difficult to determine the concentration ratio in
the breath of the patient with high accuracy.
[0009] There have been known methods for determining the
concentration ratio of .sup.13CO.sub.2 to .sup.12CO.sub.2 by way of
infrared spectroscopy (see Japanese Examined Patent Publications
No. 61-42219 (1986) and No. 61-42220 (1986)).
[0010] In the method disclosed in Japanese Examined Patent
Publication No. 61-42220, two cells respectively having a long path
and a short path are provided, the path lengths of which are
adjusted such that the light absorption by .sup.13CO.sub.2 in one
cell is equal to the light absorption by .sup.12CO.sub.2 in the
other cell. Light beams transmitted through the two cells are led
to the detectors, in which the light intensities are measured at
wavelengths which ensure the maximum sensitivity. In accordance
with this method, the light absorption ratio for the concentration
ratio of .sup.13CO.sub.2 to .sup.12CO.sub.2 in naturally occurring
carbon dioxide can be adjusted to 1. If the concentration ratio is
changed, the light absorption ratio also changes by the amount of a
change in the concentration ratio. Thus, the change in the
concentration ratio can be determined by measuring the change in
the light absorption ratio.
DISCLOSURE OF THE INVENTION
[0011] A. However, the method for determining the concentration
ratio according to the aforesaid literature suffers from the
following drawback.
[0012] Calibration curves for determining the concentrations of
.sup.12CO.sub.2 and .sup.13CO.sub.2 should be prepared by using gas
samples each having a known .sup.12CO.sub.2 concentration and gas
samples each having a known .sup.13CO.sub.2 concentration.
[0013] To prepare the calibration curve for the .sup.12CO.sub.2
concentration, the .sup.12CO.sub.2 absorbances are measured for
different .sup.12CO.sub.2 concentrations. The .sup.12CO.sub.2
concentrations and the .sup.12CO.sub.2 absorbances are plotted as
abscissa and ordinate, respectively, and the calibration curve is
determined by the method of least squares.
[0014] The calibration curve for the .sup.13CO.sub.2 concentration
is prepared in the same manner as described above.
[0015] The .sup.13CO.sub.2 concentration or the .sup.13CO.sub.2
concentration ratio (which is herein meant by .sup.13CO.sub.2
concentration/.sup.12CO.sub.2 concentration) in the breath as a
test gas sample is typically determined by way of infrared
spectroscopy. In this case, since a test sample gas, or breath is
exhaled from a living body as a result of the metabolism, the
breath contains water vapor in a concentration proximate to
saturation.
[0016] In the infrared spectroscopy, the absorption of infrared
radiation with a particular wavelength by a test gas sample is
utilized for determination of the absorbance for the test gas
sample. Since water exhibits its light absorption characteristic
over a wide range of the infrared region of the radiation spectrum,
the infrared radiation absorption by water overlaps the infrared
radiation absorption by .sup.12CO.sub.2 and .sup.13CO.sub.2. This
may cause a measurement error.
[0017] FIG. 5 is a graph obtained by plotting the measured values
of the .sup.13CO.sub.2 concentration ratio changes with respect to
the humidities of test gas samples having different humidities
ranging from 0% to 100% wherein the .sup.13CO.sub.2 concentration
ratio with respect to a 0%-humidity gas sample is used as a
reference gas sample.
[0018] As can be seen from the graph, the measured values of the
.sup.13CO.sub.2 concentration ratio are not the same, but vary
depending on the humidity.
[0019] Therefore, if the .sup.13CO.sub.2 concentration or the
.sup.13CO.sub.2 concentration ratio of a test gas sample containing
moisture is measured in ignorance of this fact, the measured value
is apparently greater than the true value.
[0020] One approach to this problem is to remove the moisture
contained in the breath sample as the test gas sample through
molecular sieving or with the use of a moisture absorbent such as
magnesium perchlorate prior to the measurement. However, some
problems may be encountered in this approach since the approach
requires a large space for housing the moisture absorbent, there is
no means for checking if the moisture is completely removed by the
moisture absorbent, and the moisture absorbent should periodically
be replaced with a new one.
[0021] It is, therefore, an object of the present invention to
provide a stable isotope measurement method and apparatus for
spectrometrically analyzing an isotopic gas, wherein a test gas
sample containing carbon dioxide .sup.13CO.sub.2 as a component gas
is introduced into a cell and the concentration or concentration
ratio of the component gas is precisely measured and corrected by
measuring moisture content in the test gas sample.
[0022] A stable isotope measurement method for spectrometrically
analyzing an isotopic gas in accordance with the present invention
comprises: a first step of introducing a test gas sample into a
cell and determining the absorbance of light transmitted
therethrough at a wavelength suitable for the component gas
.sup.13CO.sub.2; a second step of determining a concentration of
the component gas in the test gas sample on the basis of a
calibration curve prepared through measurement on test gas samples
each containing the component gas in a known concentration; and a
third step of measuring a concentration of water vapor contained in
the test gas sample and correcting a concentration of the component
gas contained in the test gas sample in accordance with the
measured water vapor concentration on the basis of a correction
curve prepared through measurement on test gas samples each
containing water vapor in a known concentration (claim 1).
[0023] A stable isotope measurement method for spectrometrically
analyzing an isotopic gas in accordance with the present invention
comprises: a first step of introducing a test gas sample containing
carbon dioxide .sup.12CO.sub.2 and carbon dioxide .sup.13CO.sub.2
as component gases into a cell and determining the absorbances of
light transmitted therethrough at wavelengths suitable for the
respective component gases; a second step of determining a
concentration ratio between the component gases in the test gas
sample on the basis of a calibration curve prepared through
measurement on test gas samples each containing the component gases
in known concentrations; and a third step of measuring a
concentration of water vapor contained in the test gas sample and
correcting a concentration ratio between the component gases
contained in the test gas sample in accordance with the measured
water vapor concentration on the basis of a correction curve
prepared through measurement on test gas samples each containing
water vapor in a known concentration (claim 2).
[0024] When compared with the prior art method, each of the
aforesaid methods additionally include the third step in which the
concentration ratio of the component gas is corrected in accordance
with the measured water vapor concentration on the basis of the
correction curve prepared through the measurement on the test gas
samples each containing water vapor in a known concentration.
[0025] Although the concentration of the component gas should
basically be represented by a single true value, the measured value
of the concentration of the component gas varies depending on the
water vapor concentration. In view of this fact, the aforesaid
methods improve the measurement accuracy of the concentration ratio
of the component gas.
[0026] The water vapor concentration may otherwise be determined by
means of any of various humidity sensors, or may be calculated from
the absorbance determined spectrometrically on the basis of the
water molecule spectrum.
[0027] In the method of claim 2, the correction curve in the third
step is prepared by determining the light absorbances at the
wavelengths suitable for the respective component gases for the
plurality of test gas samples containing water vapor in different
concentrations, then determining the concentrations of or
concentration ratios between the respective component gases in the
test gas samples on the basis of the calibration curve, and
plotting ratios or differences between the concentrations of or the
concentration ratios between the respective component gases in the
gas samples thus determined with respect to the water vapor
concentrations, and the correction in the third step is achieved by
obtaining a concentration correction value or a concentration ratio
correction value for the component gases by fitting the water vapor
concentration of the test sample gas obtained in the third step to
the correction curve, and then dividing the concentrations of or
the concentration ratio between the respective component gases in
the test gas sample obtained in the second step by the
concentration correction value or the concentration ratio
correction value obtained on the basis of the correction curve, or
subtracting the concentration correction value or the concentration
ratio correction value from the concentrations of or the
concentration ratio between the respective component gases in the
test gas sample (claim 3).
[0028] A stable isotope measurement apparatus for spectrometrically
analyzing an isotopic gas in accordance with the present invention
is a measurement apparatus adapted to perform the aforesaid methods
for spectrometrically analyzing the isotopic gas and comprises, as
data processing means, absorbance calculation means for determining
the absorbances of light transmitted through the test gas sample
introduced into the cell on the basis of light intensities measured
at the wavelengths suitable for the respective component gases,
concentration calculation means for determining the concentration
ratio of the component gases on the basis of the calibration curve
prepared through the measurement on the test gas samples each
containing the component gases in known concentrations, water vapor
concentration measuring means for measuring the concentration of
water vapor contained in the test gas sample, and correction means
for correcting the concentration ratio between the component gases
in the test gas sample in accordance with the measured water vapor
concentration on the basis of the correction curve prepared through
the measurement on the gas samples each containing water vapor in a
known concentration (claim 4).
[0029] In the methods or apparatus for spectrometrically analyzing
the isotopic gas in accordance with the present invention, when a
test gas sample containing carbon dioxide .sup.13CO.sub.2 as a
component gas is introduced into the cell and then
spectrometrically analyzed; the concentration ratio of the
component gas is corrected in accordance with the water vapor
concentration in the test gas sample. Therefore, the concentration
ratio of the component gas can be determined with a higher
accuracy.
[0030] B. In the infrared spectrometric analysis, the
.sup.12CO.sub.2 concentration in a breath sample obtained before
the drug administration is calculated from the measured
.sup.12CO.sub.2 absorbance on the basis of a .sup.12CO.sub.2
calibration curve, while the .sup.13CO.sub.2 concentration in the
breath sample is calculated from the measured .sup.13CO.sub.2
absorbance on the basis of a .sup.13CO.sub.2 calibration curve. The
.sup.12CO.sub.2 and .sup.13CO.sub.2 concentrations in the breath
sample obtained after the drug administration are determined in the
same manner.
[0031] If the CO.sub.2 concentrations in the two breath samples are
substantially the same, it is possible to use narrower ranges of
the .sup.12CO.sub.2 calibration curve and the .sup.13CO.sub.2
calibration curve. Thus, the measurement accuracy can be improved
by using limited ranges of the calibration curves.
[0032] For equalization of the CO.sub.2 concentrations in the two
breath samples, either one of the breath samples should be diluted.
Typically used as a gas for dilution (hereinafter referred to as
"diluent gas") is nitrogen gas which exhibits no absorption in the
infrared region of the radiation spectrum (nitrogen gas is used as
the diluent gas in the embodiment of the invention disclosed in
Japanese Unexamined Patent Publication No. 8-58052 (1996) which was
filed prior to the present invention).
[0033] In this dilution method, however, the diluted breath sample
has a different component gas ratio from the undiluted breath
sample, because diluent gas contains only nitrogen but breath
sample contains oxygen, moisture and etc. as well as nitrogen.
[0034] As a result, the difference in the component gas ratio
influences the determination of the .sup.13CO.sub.2 concentration
and the concentration ratios between .sup.12CO.sub.2 and
.sup.13CO.sub.2, so that the measured values may be erroneous.
[0035] It is, therefore, another object of the present invention to
provide a method for spectrometrically analyzing an isotopic gas,
wherein a breath sample as a test gas sample containing a plurality
of component gases is introduced into a cell and the concentrations
of the component gases are precisely measured through spectrometry
by diluting the test gas sample in such a manner that the component
gas composition in the test gas sample is not changed.
[0036] To achieve this object, there is provided a stable isotope
measurement method for spectrometrically analyzing an isotopic gas,
wherein two test gas samples are sampled from a single subject and,
if the CO.sub.2 concentration of one of the test gas samples is
higher than the CO.sub.2 concentration of the other test gas
sample, the one test gas sample is diluted with air (atmospheric
air) to a CO.sub.2 concentration level which is equivalent to that
of the other test gas sample for measurement of the concentration
ratios .sup.13CO.sub.2/.sup.12CO.sub.2 in the respective test gas
samples (claim 5).
[0037] In this method, the two breath samples are analyzed on
condition that the breath samples have the same CO.sub.2
concentration level. This makes it possible to use limited ranges
of the calibration curves. In addition, the component gas
composition in the breath sample is not changed by the dilution
because air is used as the diluent gas. As a result, the
measurement accuracy can be improved.
[0038] Methods according to present claims 6 and 7 each provide a
more specific procedure for the method for spectrometrically
analyzing the isotopic gas in accordance with claim 5, and are each
based on the precondition that a first test gas sample is first
filled in a single cell for measurement of the intensity of light
transmitted therethrough and, after the first test gas sample is
discharged from the cell, a second test gas sample is filled in the
cell for measurement of the intensity of light transmitted
therethrough.
[0039] As described above, the CO.sub.2 concentrations in the two
test gas samples can be generally equalized by diluting either one
of the two test gas samples so as not to change the component gas
composition of the breath sample. This makes it possible to use
limited ranges of the .sup.12CO.sub.2 and .sup.13CO.sub.2
calibration curves. The accuracy of the calibration curves is
increased as the ranges of the calibration curves to be used are
narrowed. Therefore, the measurement accuracy can be improved by
limiting the ranges of the calibration curves to be used.
DESCRIPTION OF DRAWINGS
[0040] FIG. 1 is a block diagram illustrating the overall
construction of an apparatus for spectrometrically analyzing an
isotopic gas.
[0041] FIGS. 2A to 2D are diagrams illustrating gas flow paths in
the apparatus for spectrometrically analyzing the isotopic gas.
Particularly, FIGS. 2A and 2C are diagrams illustrating gas flow
paths to be employed when a cell is cleaned by passing a clean
reference gas therethrough. FIG. 2B is a diagram illustrating gas
flow path to be employed when a base gas is sucked into a gas
injector 21 from a breath sampling bag and then mechanically pushed
out into the gas flow path at a constant rate. FIG. 2D is a diagram
illustrating a gas flow path to be employed when a sample gas is
sucked into the gas injector 21 from a breath sampling bag and then
mechanically pushed out into the gas flow path at a constant
rate.
[0042] FIGS. 3A to 3E are diagrams illustrating gas flow paths in
the apparatus for spectrometrically analyzing the isotopic gas.
Particularly, FIGS. 3A and 3D are diagrams illustrating gas flow
paths to be employed when a cell is cleaned by passing a clean
reference gas therethrough. FIG. 3B-1 is a diagram illustrating a
gas flow path to be employed when a predetermined amount of the
reference gas is sucked into the gas injector 21. FIG. 3B-2 is a
diagram illustrating a gas flow path to be employed when a
predetermined amount of air is sucked into the gas injector 21 with
a three-way valve V4 opened to the atmospheric air. FIG. 3C is a
diagram illustrating a gas flow path to be employed when a base gas
is sucked into the gas injector 21 from a breath sampling bag and
then mechanically pushed out into the gas flow path at a constant
rate. FIG. 3E is a diagram illustrating a gas flow path to be
employed when a sample gas is sucked into the gas injector 21 from
a breath sampling bag and is mechanically injected into the gas
flow path at a constant rate.
[0043] FIG. 4 is a graph prepared in such a manner that sample
gases having different humidities and a base gas having a humidity
of 0% were prepared by mixing a CO.sub.2 gas having a predetermined
.sup.13CO.sub.2 concentration and containing no moisture and a
CO.sub.2 gas having the predetermined .sup.13CO.sub.2 concentration
and containing moisture, and differences .DELTA.V between an output
value for the humidity of the base gas and output values for the
humidities of the sample gases detected by a humidity sensor 19 and
differences between the .sup.13CO.sub.2 concentration ratio in the
base gas and the .sup.13CO.sub.2 concentration ratios in the sample
gases determined on the basis of a calibration curve were plotted
as abscissa and ordinate, respectively.
[0044] FIG. 5 is a graph illustrating a relationship between the
humidity and the .sup.13CO.sub.2 concentration ratio for the sample
gas having different humidities.
DESCRIPTION OF CARRYING OUT THE INVENTION
[0045] With reference to the attached drawings, embodiments of the
present invention will hereinafter be described which are adapted
for a case where the .sup.13CO.sub.2 concentration ratio in a
breath sample is spectrometrically determined after administration
of an urea diagnostic drug labeled with an isotope .sup.13C.
[0046] I. Breath sampling test
[0047] Before the urea diagnostic drug is administered to a
patient, breath of the patient is collected in a breath sampling
bag. The volume of the breath sampling bag is about 250 ml. Then,
the urea diagnostic drug is orally administered to the patient and,
after a lapse of 10 to 15 minutes, breath of the patient is
collected in another breath sampling bag in the same manner as in
the previous breath sampling.
[0048] The breath sampling bags obtained before and after the drug
administration are respectively attached to predetermined nozzles
of an apparatus for spectrometrically analyzing an isotopic gas,
and the following automatic control is performed.
[0049] II. Apparatus for spectrometrically analyzing isotopic
gas
[0050] FIG. 1 is a block diagram illustrating the overall
construction of the apparatus for spectrometrically analyzing the
isotopic gas.
[0051] The breath sampling bag containing the breath sample
collected after the drug administration (hereinafter referred to as
"sample gas") and the breath sampling bag containing the breath
sample collected before the drug administration (hereinafter
referred to as "base gas") are respectively attached to the
predetermined nozzles of the apparatus. The breath sampling bag
containing the base gas is connected to a valve V3 through a resin
or metal pipe (hereinafter referred to simply as "pipe"), while the
breath sampling bag containing the sample gas is connected to a
valve V2 through a pipe.
[0052] A reference gas (any gas exhibiting no absorption at a
wavelength for measurement, e.g., nitrogen gas) is supplied from a
gas tank to the apparatus. The reference gas flows through a
pressure release valve 31, a valve V0, a regulator 32 and a flow
meter 33, and is diverged into a reference cell 11c through a
needle valve 35 and into a first sample cell 11a for measuring the
.sup.12CO.sub.2 absorbance through a valve V1 and a check valve
36.
[0053] A gas injector 21 (volume: 70 cc) for quantitatively
injecting the sample gas or the base gas is connected to a flow
path between the valve V1 and the first sample cell 11a via a
three-way valve V4. The gas injector 21 is a syringe-like device
having a piston and a cylinder. The piston is driven by cooperation
of a motor M1, a feed screw connected to the motor M1 and a nut
fixed to the piston.
[0054] As shown in FIG. 1, a cell chamber 11 has the first sample
cell 11a having a shorter length for measuring a .sup.12CO.sub.2
absorbance, a second shorter cell 11b having a longer length for
measuring a .sup.13CO.sub.2 absorbance, and the reference cell 11c
through which the reference gas is passed. The first sample cell
11a communicates with the second sample cell 11b. Gas is introduced
into the first sample cell 11a and then into the second sample cell
11b, and discharged therefrom. The reference gas is introduced into
the reference cell 11c. Then, a portion of the reference gas flows
into a case 10 housing the cell chamber 11 and discharged
therefrom, and the other portion of the reference gas flows into an
infrared radiation source device L and discharged therefrom.
Specifically, the first and second sample cells 11a and 11b have
lengths of 13 mm and 250 mm, respectively, and the reference cell
11c has a length of 236 mm.
[0055] A discharge pipe extending from the second sample cell 11b
is provided with an O.sub.2 sensor 18 and a humidity sensor 19.
Usable as the O.sub.2 sensor 18 are commercially available oxygen
sensors, for example, a solid electrolyte gas sensor such as a
zirconia sensor and an electrochemical gas sensor such as a
galvanic cell sensor. Usable as the humidity sensor 19 are
commercially available sensors such as utilizing a porous ceramic
resistor and a polymer resistor.
[0056] The infrared radiation source device L has two waveguides
23a and 23b for guiding an infrared beam. The generation of the
infrared radiation may be achieved arbitrarily, for example, a
ceramic heater (surface temperature: 450.degree. C.) and the like
can be used. A rotary chopper 22 for periodically blocking and
passing the infrared beams is provided adjacent to the infrared
radiation source device L. A light path along which an infrared
beam emitted from the infrared radiation source device L is
transmitted though the first sample cell 11a and the reference cell
11c is herein referred to as "first light path", while a light path
along which an infrared beam is transmitted through the second
sample cell 11b is herein referred to as "second light path".
[0057] A reference character D denotes an infrared beam detector
for detecting the infrared beams transmitted through the cells. The
infrared beam detector D has a first interference filter 24a and a
first detection element 25a disposed in the first light path, and a
second interference filter 24b and a second detection element 25b
disposed in the second light path.
[0058] The first interference filter 24a (band width: about 20 nm)
transmits infrared radiation having a interference of about 4,280
nm for measurement of the .sup.12CO.sub.2 absorbance. The second
interference filter 24b (band width: about 50 nm) transmits
infrared radiation having a wavelength of about 4,412 nm for
measurement of the .sup.13CO.sub.2 absorbance. Usable as the first
and second detection elements 25a and 25b are any elements capable
of detecting infrared radiation, for example, a semiconductor
infrared sensor such as of PbSe.
[0059] The first interference filter 24a and the first detection
element 25a are housed in a package 26a filled with an inert gas
such as Ar. Similarly, the second interference filter 24b and the
second detection element 25b are housed in a package 26b filled
with an inert gas.
[0060] The whole infrared beam detector D is maintained at a
constant temperature (25.degree. C.) by means of a heater and a
Peltier element 27. The detection elements in the packages 26a and
26b are kept at 0.degree. C. by means of a Peltier element.
[0061] The cell chamber 11 is formed of a stainless steel, and
vertically or laterally sandwiched between heaters 13.
[0062] The cell chamber 11 has two tiers. The first sample cell 11a
and the reference cell 11c are disposed in one tier, and the second
sample cell 11b is disposed in the other tier. The first light path
extends through the first sample cell 11a and the reference cell
11c which are disposed in series, and the second light path extends
through the second sample cell 11b. Reference characters 15, 16 and
17 denote sapphire transmission windows through which the infrared
radiation is transmitted.
[0063] The cell chamber 11 is kept at a constant temperature
(40.degree. C.) by controlling the heaters 13.
[0064] III. Measuring procedure
[0065] In the measurement, the CO.sub.2 concentrations of the base
gas and the sample gas are adjusted to substantially the same
level. For this purpose, the CO.sub.2 concentrations of the base
gas and the sample gas are measured in a preliminary measurement.
If the preliminarily measured CO.sub.2 concentration of the base
gas is higher than the preliminarily measured CO.sub.2
concentration of the sample gas, the CO.sub.2 concentration of the
base gas is measured after the base gas is diluted to a CO.sub.2
concentration level equivalent to that of the sample gas, and then
the CO.sub.2 concentration of the sample gas is measured in a main
measurement.
[0066] If, in the main measurement, the preliminarily measured
CO.sub.2 concentration of the base gas is lower than the
preliminarily measured CO.sub.2 concentration of the sample gas,
the CO.sub.2 concentration of the base gas is measured as it is,
and the CO.sub.2 concentration of the sample gas is measured after
the sample gas is diluted to a CO.sub.2 concentration level
equivalent to that of the base gas.
[0067] The measuring procedure includes reference gas measurement,
preliminary base gas measurement, reference gas measurement,
preliminary sample gas measurement, reference gas measurement, base
gas measurement, reference gas measurement, sample gas measurement
and reference gas measurement which are to be performed in this
order.
[0068] III-1. Preliminary base gas measurement
[0069] The gas flow path and the cell chamber 11 in the apparatus
for spectrometrically analyzing the isotopic gas are cleaned by
passing the clean reference gas therethrough, and a reference light
intensity is measured.
[0070] More specifically, the reference gas is sucked into the gas
injector 21 with the three-way valve V4 opened to the side of the
cell chamber 11 and with the valve V1 opened as shown in FIG. 2A,
and then mechanically pushed out into the flow path from the gas
injector 21 with the valve V1 closed to clean the first sample cell
11a and the second sample cell 11b. The reference gas is constantly
passed through the reference cell 11c.
[0071] In turn, the base gas is sucked into the gas injector 21
from the breath sampling bag with the valve V3 opened as shown in
FIG. 2B, and then mechanically pushed out into the flow path from
the gas injector 21 at a constant flow rate. At this time, the
intensity of light transmitted through the base gas is measured by
means of the detection elements 25a and 25b, and the CO.sub.2
concentration of the base gas is determined from its absorbance on
the basis of a calibration curve.
[0072] III-2. Preliminary sample gas measurement
[0073] The gas flow path and the cell chamber 11 in the apparatus
for spectrometrically analyzing the isotopic gas are cleaned by
passing the clean reference gas therethrough, and a reference light
intensity is measured.
[0074] More specifically, the reference gas is sucked into the gas
injector 21 with the valve V1 opened as shown in FIG. 2C, and then
pushed out into the flow path from the gas injector 21 with the
valve V1 closed to clean the first sample cell 11a and the second
sample cell 11b.
[0075] In turn, the sample gas is sucked into the gas injector 21
from the breath sampling bag with the valve V2 opened as shown in
FIG. 2D, and then mechanically pushed out into the flow path from
the gas injector 21 at a constant flow rate. At this time, the
intensity of light transmitted through the sample gas is measured
by means of the detection elements 25a and 25b, and the CO.sub.2
concentration of the sample gas is determined from its absorbance
on the basis of the calibration curve.
[0076] III-3. Reference measurement
[0077] The gas flow path is changed, and then the reference gas is
passed therethrough to clean the gas flow path and the cell chamber
11. After a lapse of about 30 seconds, light intensities are
measured by means of each of the detection elements 25a and
25b.
[0078] More specifically, the reference gas is sucked into the gas
injector 21 with the valve V1 opened as shown in FIG. 3A, and then
pushed out into the flow path from the gas injector 21 with the
valve V1 closed to clean the first sample cell 11a and the second
sample cell 11b. At this time, the intensities of light transmitted
through the reference gas are measured by means of the detection
element 25a and the detection element 25b. The light intensities
thus obtained by the first and second detection elements 25a and
25b are represented by .sup.12R.sub.1 and .sup.13R.sub.1,
respectively.
[0079] III-4. Base gas measurement
[0080] The CO.sub.2 concentration of the base gas obtained by the
first detection element 25a in "III-1. Preliminary base gas
measurement" is compared with the CO.sub.2 concentration of the
sample gas obtained by the first detection element 25a in "III-2.
Preliminary sample gas measurement". If the CO.sub.2 concentration
of the base gas is higher than the CO.sub.2 concentration of the
sample gas, the base gas is diluted with the air or reference gas
in the gas injector 21 to a CO.sub.2 concentration level equivalent
to that of the sample gas, and then the light intensity measurement
is performed on the base gas thus diluted.
[0081] More specifically, a predetermined amount of the reference
gas is sucked into the gas injector 21 with the valve V1 opened as
shown in FIG. 3B-1. In turn, the base gas is sucked into the gas
injector 21 with the valve V3 opened as shown in FIG. 3C, and mixed
with the reference gas. Since the CO.sub.2 concentrations of the
two breath samples are adjusted to substantially the same level by
thus diluting the base gas with the reference gas, the ranges of
the .sup.12CO.sub.2 and .sup.13CO.sub.2 calibration curves to be
used can be narrowed.
[0082] Alternatively, a predetermined amount of air may be sucked
into the gas injector 21 with the three-way valve V4 opened to the
atmospheric air as shown in FIG. 3B-2. In turn, the base gas is
sucked into the gas injector 21 with the three-way valve V4 opened
to the cell chamber and with the valve V3 opened as shown in FIG.
3C, and then mixed with the air.
[0083] Since the CO.sub.2 concentrations of the two breath samples
are adjusted to substantially the same level by thus diluting the
base gas with the air, the ranges of the .sup.12CO.sub.2 and
.sup.13CO.sub.2 calibration curves to be used can be narrowed.
[0084] It should be noted that the measuring procedure employing
the dilution method shown in FIG. 3B-2 is characterized in that the
CO.sub.2 concentrations of the two breath samples are adjusted to
substantially the same level, and does not necessarily require to
employ a step of constantly maintaining the CO.sub.2 concentration
at a constant level as described in Japanese Examined Patent
Publication No. 4-124141 (1992). The use of limited ranges of the
calibration curves can be achieved simply by adjusting the CO.sub.2
concentrations of the base gas and the sample gas to substantially
the same level. Since the CO.sub.2 concentrations of the base gas
and the sample gas may vary within a range of 1% to 6% in actual
measurement, it is very troublesome to always maintain the CO.sub.2
concentrations at a constant level.
[0085] If the CO.sub.2 concentration of the base gas is lower than
the CO.sub.2 concentration of the sample gas, the base gas is not
diluted, but the base gas is subjected to the measurement as it
is.
[0086] The base gas is mechanically pushed out into the flow path
from the gas injector 21 at a constant flow rate and, at this time,
light intensity measurement is performed by means of the detection
elements 25a and 25b.
[0087] The light intensities thus obtained by the first and second
detection elements 25a and 25b are represented by .sup.12B and
.sup.13B, respectively.
[0088] III-5. Reference measurement
[0089] The cleaning of the gas flow path and the cells and the
light intensity measurement on the reference gas are performed
again by employing the flow path shown in FIG. 3D.
[0090] The light intensities thus obtained by the first and second
detection elements 25a and 25b are represented by .sup.12R.sub.2
and .sup.13R.sub.2, respectively.
[0091] III-6. Sample gas measurement
[0092] If the base gas is diluted in "III-4. Base gas measurement",
the sample gas is sucked into the gas injector 21 from the breath
sampling bag as shown in FIG. 3E, and then mechanically pushed out
into the flow path from the gas injector 21 at a constant flow
rate. At this time, light intensities are measured by the detection
elements 25a and 25b.
[0093] If the base gas is not diluted in "III-4. Base gas
measurement", the sample gas is diluted with the reference gas or
air to a CO.sub.2 concentration level equivalent to that of the
base gas in the gas injector 21, and then the intensities of light
transmitted through the sample gas is measured by means of the
detection elements 25a and 25b.
[0094] The light intensities thus obtained by the first and second
detection elements 25a and 25b are represented by .sup.12S and
.sup.13S, respectively.
[0095] III-7. Reference gas measurement
[0096] The cleaning of the gas flow path and the cells and the
light intensity measurement on the reference gas are performed
again.
[0097] The light intensities thus obtained by the first and second
detection elements 25a and 25b are represented by .sup.12R.sub.3
and .sup.13R.sub.3, respectively.
[0098] IV. Data processing
[0099] IV-1. Calculation of absorbances of base gas
[0100] The .sup.12CO.sub.2 absorbance .sup.12Abs(B) and the
.sup.13CO.sub.2 absorbance .sup.13Abs(B) of the base gas are
calculated on the basis of the transmitted light intensities
.sup.12R.sub.1 and .sup.13R.sub.1 for the reference gas, the
transmitted light intensities .sup.12B and .sup.13B for the base
gas and the transmitted light intensities .sup.12R.sub.2 and
.sup.13R.sub.2 for the reference gas obtained in accordance with
the aforesaid measuring procedure.
[0101] The .sup.12CO.sub.2 absorbance .sup.12Abs(B) is calculated
from the following equation:
.sup.12Abs(B)=-log[2.times..sup.12B/(.sup.12R.sub.1+.sup.12R.sub.2)]
[0102] The .sup.13CO.sub.2 absorbance .sup.13Abs(B) is calculated
from the following equation:
.sup.13Abs(B)=-log[2.times..sup.13B/(.sup.13R.sub.1+.sup.13R.sub.2)]
[0103] Since the calculation of the absorbances is based on the
light intensities obtained in the base gas measurement and the
averages (R.sub.1+R.sub.2)/2 of the light intensities obtained in
the reference measurements performed before and after the base gas
measurement, the influence of a drift (a time-related influence on
the measurement) can be eliminated. Therefore, when the apparatus
is turned on, there is no need for waiting until the apparatus
reaches a complete thermal equilibrium (it usually takes several
hours), so that the measurement can be started immediately after
the turn-on of the apparatus.
[0104] IV-2. Calculation of absorbances of sample gas
[0105] The .sup.12CO.sub.2 absorbance .sup.12Abs(S) and the
.sup.13CO.sub.2 absorbance .sup.13Abs(S) of the sample gas are
calculated on the basis of the transmitted light intensities
.sup.12R.sub.2 and .sup.13R.sub.2 for the reference gas, the
transmitted light intensities .sup.12S and .sup.13S for the sample
gas and the transmitted light intensities .sup.12R.sub.3 and
.sup.13R.sub.3 for the reference gas obtained in accordance with
the aforesaid measuring procedure.
[0106] The .sup.12CO.sub.2 absorbance .sup.12Abs(S) is calculated
from the following equation:
.sup.12Abs(S)=-log[2.times..sup.12S/(.sup.12R.sub.2+.sup.12R.sub.3)]
[0107] The .sup.13CO.sub.2 absorbance .sup.13Abs(S) is calculated
from the following equation:
.sup.13Abs(S)=-log[2.times..sup.13S/(.sup.13R.sub.2+.sup.13R.sub.3)]
[0108] Since the calculation of the absorbances is based on the
light intensities obtained in the sample gas measurement and the
averages of the light intensities obtained in the reference
measurements performed before and after the sample gas measurement,
the influence of a drift can be eliminated.
[0109] IV-3. Calculation of concentrations
[0110] The .sup.12CO.sub.2 concentration and the .sup.13CO.sub.2
concentration are calculated by using calibration curves.
[0111] The calibration curves are prepared on the basis of
measurement performed by using test gas samples of known
.sup.12CO.sub.2 concentrations and test gas samples of known
.sup.13CO.sub.2 concentrations.
[0112] For preparation of the calibration curve for
.sup.12CO.sub.2, the .sup.12CO.sub.2 absorbances for different
.sup.12CO.sub.2 concentrations ranging from about 0.5% to about 6%
are measured. The .sup.12CO.sub.2 concentrations and the
.sup.12CO.sub.2 absorbances are plotted as abscissa and ordinate,
respectively, and an approximate curve is determined by the method
of least squares. An approximate quadratic curve, which includes
relatively small errors, is employed as the calibration curve in
this embodiment.
[0113] For preparation of the calibration curve for
.sup.13CO.sub.2, the .sup.13CO.sub.2 absorbances for different
.sup.13CO.sub.2 concentrations ranging from about 0.006% to about
0.07% are measured. The .sup.13CO.sub.2 concentrations and the
.sup.13CO.sub.2 absorbances are plotted as abscissa and ordinate,
respectively, and an approximate curve is determined by the method
of least squares. An approximate quadratic curve, which includes
relatively small errors, is employed as the calibration curve in
this embodiment.
[0114] Strictly speaking, the .sup.13CO.sub.2 absorbance determined
by individually measuring a gas sample containing .sup.12CO.sub.2
and a gas sample containing .sup.13CO.sub.2 may be different from
the .sup.13CO.sub.2 absorbance determined by measuring a gas sample
containing both .sup.12CO.sub.2 and .sup.13CO.sub.2. This is
because the interference filters each have a certain bandwidth and
the .sup.12CO.sub.2 absorption spectrum partially overlaps the
.sup.13CO.sub.2 absorption spectrum. Since gas samples containing
both .sup.12CO.sub.2 and .sup.13CO.sub.2 are to be analyzed in this
measurement method, the overlap of these spectra should be
corrected in determination of the calibration curves. The
calibration curves to be employed in this measurement are corrected
for the overlap of the absorption spectra.
[0115] The .sup.12CO.sub.2 concentration and .sup.13CO.sub.2
concentration of the base gas and the .sup.12CO.sub.2 concentration
and .sup.13CO.sub.2 concentration of the sample gas determined by
using the aforesaid calibration curves are represented by
.sup.12Conc(B), .sup.13Conc(B), .sup.12Conc(S) and .sup.13Conc(S),
respectively.
[0116] IV-4. Calculation of concentration ratios
[0117] The concentration ratio of .sup.13CO.sub.2 to
.sup.12CO.sub.2 is determined. The concentration ratios in the base
gas and in the sample gas are expressed as
.sup.13Conc(B)/.sup.12Conc(B) and .sup.13Conc(S)/.sup.12Conc(S),
respectively.
[0118] Alternatively, the concentration ratios in the base gas and
in the sample gas may be defined as
.sup.13Conc(B)/[.sup.12Conc(B)+.sup.13Conc(B- )] and
.sup.13Conc(S)/[.sup.12Conc(S)+.sup.13Conc(S)], respectively. Since
the .sup.12CO.sub.2 concentration is much higher than the
.sup.13CO.sub.2 concentration, the concentration ratios expressed
in the former way and in the latter way are substantially the
same.
[0119] IV-5. Determination of .sup.13C change
[0120] A .sup.13C difference between the sample gas and the base
gas is calculated from the following equation:
.DELTA..sup.13C=[Concentration ratio of sample gas-Concentration
ratio of base gas].times.10.sup.3/Concentration ratio of base gas
(Unit: per mill (per thousand))
[0121] IV-6. Correction of .sup.13C change
[0122] The difference .DELTA..sup.13C in the .sup.13CO.sub.2
concentration ratio between the base gas and the sample gas is
subjected to a correction for water vapor concentration (correction
for humidity) according to the present invention.
[0123] For this purpose, the difference .DELTA..sup.13C in the
.sup.13CO.sub.2 concentration ratio is corrected with the use of a
graph prepared by plotting difference .DELTA..sup.13C in the
.sup.13CO.sub.2 concentration ratios with respect to outputs of the
humidity sensor 19.
[0124] More specifically, the preparation of the graph is achieved
in the following manner. A 3% CO.sub.2/N.sub.2 balance gas having a
humidity of 0% is filled in two gas sampling bags, and water vapor
is charged to saturation into one of the gas sampling bag for
preparation of a 3% CO.sub.2/N.sub.2 balance gas having a humidity
of 100%. By mixing these two gases, five sample gases having
different humidities ranging from 0% to 100% and a base gas having
a humidity of 0% is prepared. An output of the humidity sensor 19
indicative of the humidity of the base gas and outputs of the
humidity sensor 19 indicative of the humidities of the sample gases
are obtained. The differences .DELTA.V between the output for the
base gas and the outputs for the sample gases are plotted as
abscissa. Since the humidity of the base gas is 0%, the differences
.DELTA.V in the output correspond to values indicative of the
humidities of the sample gases. Then, the differences in the
.sup.13CO.sub.2 concentration between the base gas and the sample
gases are plotted as ordinate. Thus, the preparation of the graph
is completed.
[0125] Experimentally obtained values are shown in Table 1.
1TABLE 1 Humidity of Sensor Sensor Difference Difference in sample
gas output of output of in sensor .sup.13CO.sub.2 concent- (%) base
gas sample gas output ration ratio (0/00) 0 1.653168 1.541812
-0.111356 -0.2 25 1.789176 2.407378 0.618202 2.34 50 1.925964
3.117390 1.191426 4.28 75 2.022190 3.594348 1.572158 5.60 100
2.110666 3.970968 1.860302 5.32
[0126] Although the outputs of the sensor indicative of the
humidity of the base gas should basically be the same level, the
measured output values varied with a drift. This is because the
response speed of the humidity sensor 19 was problematic and the
measurement was performed before the humidity sensor 19 did not
reach complete equilibrium. The values in Table 1 are plotted as
shown in a graph of FIG. 4.
[0127] The differences .DELTA..sup.13C in the .sup.13CO.sub.2
concentration ratio between the base gas and the sample gases are
corrected on the basis of the graph and the differences in the
output of the humidity sensor 19 between the base gas and the
sample gases.
* * * * *